Antioxidant Approach of Nigella Sativa, Vit C and Silymarin for amelioration of Azithromycin induced Hepatotoxicity: Histological, Immunohistochemical and Biochemical study

Abstract The recent outbreak of SARS CoV-2 has changed the global scenario of human lives and economy. In this pandemic-outbreak the ratio of infected person is much higher than the death encountered. Most of the dead patients were observed with dysfunction/failure of cardiac and renal systems. Beside this a ‘cytokine storm’ namely TNF-α/IL1 receptors i.e. TNFR1/TNFR2/IL1R over-functioning was reported in the infected-persons. Here, nigellidine, an indazole-alkaloid and key-component of Nigella Sativa L. (NS); black-cumin-seed, has been analyzed for COVID-19 different protein and TNFα receptors TNFR1/TNFR2 and IL1R inhibition through molecular-docking study and biochemical-study of cumin-seed extract exposure to experimental-rat. The NMR, X-ray-crystallographic or Electron-microscopic structures of COVID-19 Main-protease(6LU7), Spike-glycoprotein(6vsb), NSP2(QHD43415_2), N-terminus-protenase (QHD43415_3), Nucleocapsid(QHD43423) and Human IL1R (1itb), TNFR1 (1ncf), TNFR2 (3alq) from PDB were retrieved/analyzed for receptor-ligand interaction in normal condition. Then those structures were docked with nigellidine using Autodock-software and Patchdock-server. Where nigellidine showed highest binding-energy of -7.61 (kcal/mol) and ligand-efficiency value of (-0.35) forming bonds with amino acids THR943/LYS945/MET1556/ALA1557/PRO1558/ILE1559. Highest ACE-value of -356.72 was also observed for nigellidine N-terminal-protease interaction. Nigellidine also showed strong interaction with NSP2 (-6.28) and Mpro/3CLpro_Q (-6.38s). Nigellidine showed affinity to TNFR1 (-6.81), IL1R (-6.23) and TNFR2 (-5.16). In rat experiment 2-groups (vehicle and NS treated) of female Wistar-rats were taken for experiments. The NS treated tissue showed marked decline in ALP/SGPT/ SGOT/MDA level then the basal-levels. From the Western-blot or activity analysis it was observed that Nigellidine, the sulfuryl-group containing drug showed no impact on Phenol-catalyzing ASTIV or Steroid-catalyzing EST expressions/activities and thus have no influence in sulfation-mediated adverse metabolic-processes. Current-results concluded that Nigellidine has hepato/reno-protective; immunomodulatory/anti-inflammatory and antioxidant activities as well as it inhibits important proteins of COVID-19. With steps to further validation/checking nigellidine can be used in COVID-19 infection.

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Biochemical study on the impact of Nigella sativa and virgin olive oils on cadmium-induced nephrotoxicity and neurotoxicity in rats

Journal of Investigational Biochemistry ◽

10.5455/jib.20140716041908 ◽

2014 ◽

Vol 3 (2) ◽

pp. 71 ◽

Cited By ~ 9

Author(s):

Eman Mohammed ◽

Khalid Hashem ◽

Mahmoud Rheim

Keyword(s):

Biochemical Study ◽

Nigella Sativa ◽

Virgin Olive Oils ◽

Olive Oils ◽

The Impact

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Potentiation of bromotrichloromethane hepatotoxicity in male rats exposed to 10 ppm dietary chlordecone: Electron Microscopic and biochemical study

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100158972 ◽

1990 ◽

Vol 48 (3) ◽

pp. 284-285

Author(s):

O. M. Faroon ◽

R. W. Henry ◽

M. G. Soni ◽

H. M. Mehendale

Keyword(s):

Free Radical ◽

Biochemical Study ◽

Prior Exposure ◽

Male Rats ◽

Cellular Injury ◽

Low Doses ◽

Mixed Function Oxidase ◽

Electron Microscopic ◽

Potent Inducer ◽

Cellular Energy

Previous work has shown that mirex undergoes photolytic dechlorination to chlordecone (CD) (KeponeR) in the environment. Much work has shown that prior exposure to nontoxic levels of CD causes potentiation of hepatotoxicity and lethality of CCl4, BrCCl3 and other halomethane compounds. Potentiation of bromotrichloromethane hepatotoxicity has been associated with compounds that stimulate the activity of hepatic mixed-function oxidase (MFO). An increase in the metabolism of halomethane by the MFO to a free radical initiates peroxidative decomposition of membranal lipids ending in massive cellular injury. However, not all MFO inducers potentiate BrCCl3 hepatotoxicity. Potentiation by much larger doses of phenobarbital is minimal and th at by a more potent inducer of MFO, mirex, is negligible at low doses. We suggest that the CD and bromotrichloromethane interaction results in a depletion of cellular energy and thereby reducing the cellular ability to undergo mitosis.

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Biochemical Study of the Large Molecular Constituents of Gastric Juice

Gastroenterology ◽

10.1016/s0016-5085(19)35923-2 ◽

1955 ◽

Vol 29 (6) ◽

pp. 1017-1023 ◽

Cited By ~ 18

Author(s):

Virginia Richmond ◽

Ranwel Caputto ◽

Stewart Wolf

Keyword(s):

Gastric Juice ◽

Biochemical Study

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Liver Histological Improvement After Administration of High-Dose Vitamin C in Guinea Pig with Nonalcoholic Steatohepatitis

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000515 ◽

2018 ◽

Vol 88 (5-6) ◽

pp. 263-269

Author(s):

Seong-Hoon Park ◽

A Lum Han ◽

Na-Hyung Kim ◽

Sae-Ron Shin

Keyword(s):

Liver Biopsy ◽

Vitamin C ◽

Nonalcoholic Steatohepatitis ◽

Guinea Pigs ◽

Normal Diet ◽

High Dose ◽

Biochemical Tests ◽

Deficient Diet ◽

Histological Improvement ◽

Vit C

Abstract. Background: Vitamin C is a strong antioxidant, and the health effects of vitamin C megadoses have not been validated despite the apparent health benefits. Therefore, the present study sought to confirm the effects of vitamin C megadoses. Materials and Methods : Four groups of six guinea pigs were used. Each group was fed one of the following diets for three weeks: normal diet, methionine choline-deficient diet, methionine choline-deficient diet + vitamin C megadose (MCD + vit C 2.5 g/kg/day), and methionine-choline deficient diet + ursodeoxycholic acid (MCD + UDCA 30 mg/kg/day). The MCD diet was given to induce nonalcoholic steatohepatitis, and UDCA was used to treat nonalcoholic steatohepatitis. Three weeks after initial diet administration, the results of biochemical tests and liver biopsy were compared between the groups. Results: The cytoplasm state was similar in the MCD + vit C and MCD + UDCA groups, exhibiting clearing of the cytoplasm and ballooning degeneration. However, macrovesicular steatosis was not observed in the MCD + vit C group. Aspartate transaminase and alanine transaminase were elevated significantly following vitamin C administration. Conclusions: The present study confirmed that alone vitamin C megadoses are potential remedies for nonalcoholic steatohepatitis, based on the liver biopsy results of guinea pigs that were unable to synthesize vitamin C.

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